Recent developments aragonite-based calcium carbonate nanoparticles: Advances in synthesis, therapeutic mechanisms, and oncology

Calcium carbonate (CaCO3), particularly in its aragonite polymorph is a promising biomaterial for drug delivery systems owing to its low toxicity, pH-responsive behaviour, cost-effectiveness, and intrinsic biocompatibility. This review examines recent advances in the synthesis of CaCO₃ nanoparticles (CaCO₃-NPs), focusing on their role in modulating tumour microenvironments for cancer therapy. We explore various synthesis strategies, including chemical precipitation, gas diffusion, and microemulsion methods, highlighting their effects on nanoparticle size, shape and stability. The therapeutic mechanism of (CaCO₃-NPs), such as calcium ion-induced cytotoxicity, pH responsive drug release, and CO2 production, are discussed in the context of their potential for targeted therapy, immune modulation, and multimodal diagnostics in oncology. Recent developments in CaCO3-based combinatorial nanomedicine are highlighted, including application in chemotherapy, immunotherapy, and multimodal imaging, primarily within preclinical models. In addition, key challenges associated with scalability, reproducibility, regulatory challenges and clinical translation are discussed. This review highlights the translational potential of aragonite-based CaCO3 nanocarriers and outline their potential and limitation as multifunctional platforms for precision oncology.